D-cycloserine (DCS) is an N-methyl-D-aspartate (NMDA) receptor partial agonist that facilitates extinction of
conditioned fear in animals and cue exposure therapy (CET) for fear and anxiety disorders
in people. Recent preclinical and clinical studies have examined the effect of DCS
on extinction of conditioned responses elicited by cues paired with administration
of or withdrawal from drugs of abuse, including physiological responses, craving,
withdrawal, and drug-seeking behavior. DCS facilitates extinction and blunts postextinction
recovery of these responses in animal models, including place conditioning and drug
self-administration, but DCS effects on CET in substance users/abusers are less robust.
Some of the null effects in the clinical literature might be attributable to issues
related to sample size, data characteristics, DCS administration, and participant
characteristics, among others. In this review we describe the preclinical and clinical
literatures on DCS modulation of extinction of addiction-related conditioned responses,
consider possible limitations of the clinical studies that have been published to
date, and propose ways of designing future clinical studies so as to maximize the
probability of detecting a DCS effect. We also discuss concerns with regard to potential
harmful effects of DCS-coupled CET in addicts and describe how these concerns might
be mitigated. We conclude that it is as yet unclear whether DCS-coupled CET might
be a useful approach in the treatment of addiction.
Key Words
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Article info
Publication history
Accepted:
February 18,
2012
Received in revised form:
February 14,
2012
Received:
January 11,
2012
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
